Neurophysiology & Muscle Physiology — Study Materials Summary & Study Notes

🧠 Neuron Structure and Zones

Neuron is the functional cell of the nervous system composed of a soma (cell body), dendrites, and an axon. The soma contains the metabolic machinery and protein synthesis organelles. Dendrites are branched processes that conduct incoming signals toward the soma, while the axon conducts impulses away from the soma and can be over 1 m long in large neurons.

⚡ Axon Hillock and Action Potential Initiation

The axon hillock is the junction between soma and axon and has the lowest threshold for generating an action potential because of a high density of $Na^{+}$ channels. Most action potentials originate at the axon hillock and propagate down the axon to axon terminals.

🔁 Axon Terminals & Synaptic Transmission

Axon terminals contain synaptic vesicles filled with neurotransmitter and many mitochondria to supply ATP for vesicle recycling and ion pumping. When an action potential arrives, voltage-gated $Ca^{2+}$ channels open; influx of $Ca^{2+}$ triggers vesicle exocytosis, neurotransmitter diffusion across the synaptic cleft (~30–50 nm), and activation of receptors on the postsynaptic cell.

🧩 Postsynaptic Potentials and Summation

A single synapse produces a small postsynaptic potential (PSP) (≈0.5–1 mV) which is often insufficient to reach threshold. Neurons rely on spatial summation (simultaneous inputs from many synapses) and temporal summation (rapid successive inputs from one synapse) to generate a grand postsynaptic potential large enough to trigger an action potential.

⛔ Inhibitory vs Excitatory Ion Channels

Ion channels mediate excitation or inhibition: $Na^{+}$ channels are typically excitatory, while $K^{+}$ and $Cl^{-}$ channels are typically inhibitory. Neurotransmitter binding can open ligand-gated channels directly or act indirectly via second messengers to modulate excitability or gene expression.

🔬 Major Neurotransmitters and Actions

Common neurotransmitters include acetylcholine (ACh), norepinephrine (NE), dopamine, serotonin, glutamate, GABA, nitric oxide (NO), and various neuropeptides. Some (e.g., glutamate, GABA, ACh) act at ionotropic receptors to open ion channels, while others (e.g., NE, dopamine, serotonin) often act via G-protein–coupled receptors to generate second messengers.

🧪 Uptake, Degradation and Pharmacology

Neurotransmitters are removed from the synapse by reuptake into terminals or enzymatic breakdown (e.g., acetylcholinesterase breaks down ACh; MAO and COMT degrade monoamines). Drugs and toxins modify synaptic transmission: cocaine blocks monoamine reuptake, organophosphates inhibit acetylcholinesterase, and botulinum toxin blocks ACh release.

🧾 Neuropeptides & Neuromodulation

Neuropeptides (e.g., endorphins, enkephalins, CCK) are synthesized in the soma, transported to terminals, and can function as traditional neurotransmitters or neuromodulators to produce longer-term changes in neuronal excitability and gene expression.

🧩 Glial Cells and Myelination

Glial cells include oligodendrocytes (CNS), Schwann cells (PNS), and astrocytes. Oligodendrocytes and Schwann cells form myelin sheaths that insulate axons; nodes of Ranvier are gaps where action potentials are regenerated, enabling saltatory conduction and energy savings. Astrocytes help regulate the extracellular environment, ions, neurotransmitters, and contribute to the blood–brain barrier.

🧭 CNS and PNS Divisions

The central nervous system (CNS) consists of brain and spinal cord; the peripheral nervous system (PNS) contains nerves outside the CNS. The PNS is functionally divided into the somatic nervous system (voluntary control of body wall and muscles) and the autonomic nervous system (involuntary control of viscera and blood vessels).

🔁 Autonomic Subdivisions and Neurotransmission

The sympathetic system arises from thoracolumbar regions and typically uses a two-neuron chain (preganglionic ACh → nicotinic receptor on postganglionic → NE at target via alpha/beta receptors). The parasympathetic system arises from cranial/sacral regions and usually uses ACh at both pre- and postganglionic synapses with muscarinic receptors at the effector.

🧠 Higher Brain Centers & Functions

Key CNS centers include the brainstem (basic life control centers), cerebellum (coordination and motor planning), hypothalamus (homeostasis and endocrine link), thalamus (sensory relay), and cerebral cortex (sensory perception, voluntary movement, language, personality, and higher cognition). The blood–brain barrier formed by tight endothelial junctions restricts access of many blood-borne substances to brain extracellular fluid.

💪 Muscle Organization and Fiber Types

Skeletal muscle is composed of bundles of muscle fibers (cells) that contain many myofibrils, which in turn are built from repeating sarcomeres. There are three primary fiber types: fast glycolytic (Type IIb), slow oxidative (Type I), and fast oxidative (Type IIa), differing in contraction speed, fatigue resistance, and primary energy pathways.

🧩 Sarcomere Structure and Contractile Proteins

A sarcomere is the functional unit between two Z-lines and contains thin filaments (actin) and thick filaments (myosin). Myosin heads have actin-binding and myosin ATPase active sites; tropomyosin and troponin regulate actin–myosin interactions, with troponin C binding $Ca^{2+}$ to permit contraction.

⚙️ Molecular Mechanism of Contraction (Sliding Filament)

At rest, low cytosolic $Ca^{2+}$ keeps troponin/tropomyosin covering myosin-binding sites on actin. When cytosolic $Ca^{2+}$ rises, $Ca^{2+}$ binds troponin C, causing a conformational change that exposes binding sites. Myosin heads bind actin, perform the powerstroke (releasing ADP), then bind ATP to detach; ATP hydrolysis re-cocks the head for another cycle — the repeated cycles produce filament sliding.

🔌 Neuromuscular Junction & Excitation

A motor neuron action potential causes $Ca^{2+}$-dependent release of ACh at the neuromuscular junction. ACh opens ligand-gated channels on the motor end plate producing a large end-plate potential (+50 to +70 mV) that triggers action potentials in adjacent muscle membrane, initiating contraction.

🧯 Excitation–Contraction Coupling

Action potentials travel along the sarcolemma and into T-tubules, activating the sarcoplasmic reticulum (SR) to release large amounts of $Ca^{2+}$. The SR has high $Ca^{2+}$ storage (≈10,000:1 ratio SR vs cytosol) and pumps $Ca^{2+}$ back to terminate contraction.

⏱️ Twitch, Summation and Tetanus

A single action potential yields a brief twitch (≈100 ms). Repeated action potentials can produce wave summation, where tension adds and can lead to tetanus, the sustained maximal tension state. Muscle force is also graded by motor unit recruitment — activating more motor units increases whole-muscle force.

⚡ Muscle Energy Metabolism & Fatigue

ATP fuels crossbridge cycling, $Ca^{2+}$ pumping into SR, and $Na^{+}/K^{+}$ pumps. Immediate ATP is limited (~3 s), supplemented by creatine phosphate via the phosphagen system (up to ~8–10 s), glycogen–lactic acid (anaerobic) system (up to ~1.5 min), and oxidative phosphorylation (aerobic) for sustained activity (producing ~32–36 ATP/glucose). The anaerobic threshold marks the intensity where lactate accumulates faster than it can be removed.

🧬 Muscle Plasticity and Hypertrophy

Training causes hypertrophy (increased fiber diameter), increased myofibrils, mitochondrial enzymes, phosphocreatine, and stored glycogen; fiber-type composition can influence performance and adapt to training demands.

🌀 Smooth Muscle Basics

Smooth muscle has small spindle-shaped fibers without striations, lacking troponin and with poorly developed SR; most $Ca^{2+}$ comes from extracellular fluid and binds calmodulin to activate myosin light chain kinase, enabling crossbridge cycling. Smooth muscle occurs as multiunit (neurogenic, independent units) or single-unit (functional syncytium via gap junctions, e.g., gut peristalsis).